Immune checkpoint blockade therapies for HCC: current status and future implications

作     者：Ritu Shrestha Kim R.Bridle Darrell H.G.Crawford Aparna Jayachandran Ritu Shrestha;Kim R. Bridle;Darrell H. G. Crawford;Aparna Jayachandran

作者机构：The University of QueenslandFaculty of MedicineBrisbaneQueensland 4120Australia Gallipoli Medical Research InstituteGreenslopes Private HospitalBrisbaneQueensland 4120Australia 

出 版 物：《Hepatoma Research》 (肝癌研究（英文版）)

年 卷 期：2019年第5卷第9期

页      面：1-17页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This manuscript publication is funded by Gallipoli Medical Research Foundation 

主　　题：Hepatocellular carcinoma immunotherapy immune checkpoint inhibitors epithelial-to-mesenchymal transition programmed cell death protein-1 programmed death-ligand 1 resistance 

摘      要：Hepatocellular carcinoma(HCC)is the most lethal and common type of liver cancer with limited treatment options at the advanced *** use of immune checkpoint inhibitor(ICI)based immunotherapy is exponentially increasing in the treatment of patients with advanced solid *** expression of immune checkpoints on tumor cells leading to lower activity of T-cells is one of the major mechanisms of immune *** blockade immunotherapies with antibodies against PD-1,PD-L1 or CTLA-4 are being investigated in clinical trials in HCC *** have improved survival in patients with inoperable advanced stage HCC where other curative treatments are not ***,the response rates remain low with only a small subset of patients responding to this *** is an unmet need to identify predictive markers to select those HCC patients who would benefit from ICI ***,epithelial-to-mesenchymal transition(EMT),a major process driving HCC invasion and metastasis by regulating the phenotypic cellular switching from epithelial to mesenchymal state,has been implicated as a resistance mechanism associated with ICI *** role of EMT as a regulator of immune checkpoint molecule in HCC is just ***,the consequence of EMT as a resistance mechanism in HCC patients undergoing ICI treatments remains *** this review,we summarize the recent clinical studies with ICIs in HCC and highlight the trials underway featuring novel monotherapies and combinatorial approaches based on immune and non-immune *** will discuss the ongoing efforts to discover new immune checkpoint molecules in HCC as potential drug *** also highlight the role of EMT in facilitating therapy resistance in HCC treated with ICIs and discuss potential strategies to circumvent resistance in ICI treated HCC patients.